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Biomedical subjects

J I Herrero

Publications and source records attributed to J I Herrero.

At least 19 recordsLinked to original sources

[Liver transplantation].

Liver transplantation is an efficient therapeutic option for terminal hepatic diseases. The principal indications of liver transplantation are hepatic cirrhosis, hepatic tumours (mainly, hepatocellular carcinoma) and acute liver failure. Over the years, the absolute contraindications for a transplant have lessened. Surgical techniques have also undergone changes. The results of liver transplant have improved so that survival one year after the transplant is close to 90% and after five years some 80% of transplanted patients continue to live.

Age Factors↗

Study on the efficacy and safety of adefovir dipivoxil treatment in post-liver transplant patients with hepatitis B virus infection and lamivudine-resistant hepatitis B virus.

Hepatitis B virus (HBV) recurrence and de novo HBV infection are frequent events in liver transplantation recipients. Treatment with lamivudine is initially efficient in both infections but the incidence of lamivudine-resistant HBV emergence increases over time. Adefovir appears to be promising in post-liver transplantation patients with recurrent HBV infection and lamivudine-resistant HBV. This study analyzed adefovir treatment in 42 post-liver transplantation patients who developed recurrent HBV or de novo HBV infection with lamivudine-resistant HBV (54.8% HCV-coinfected). Patients received 10 mg of oral adefovir once daily for a mean period of time of 21.5 months (range from 12 to 31 months). In 62.9% of patients, ALT levels decreased significantly. Serum HBV-DNA was undetectable in 64% of the cases. Twenty percent of patients lost HBeAg marker and 13.3% of them developed anti-HBe. In 9.5% of recipients, HBsAg became negative. There was no significant change in serum creatinine levels. In only one patient was worsening of the renal function detected, making dose adjustment necessary. No other side effects were reported. Our results confirm the efficacy and safety of adefovir treatment in post-liver transplantation patients with lamivudine-resistant HBV, neither were adefovir-resistant mutations identified in patients after 21 months of therapy, nor were there adverse events, especially renal toxicity.

Adenine↗

[Liver transplantation in patients with cirrhosis secondary to hepatitis B virus and hepatitis C virus infections].

Liver cirrhosis main related to hepatitis C virus constitutes the main indication of liver transplantation in Europe and the USA, representing as many as 50% of the indications in adults, while cirrhosis associated with hepatitis B virus represents around 10%. The indications for transplantation in patients with infection by both viruses are fulminant hepatitis, decompensated cirrhosis and hepatocellular carcinoma. Both injections may relapse after transplantation. The evolution of the relapse in the graft is variable and can include non-significant alterations of the liver junction tests, chronic active hepatitis and cirrhosis. Less frequently, a particularly severe form called "fibrosing cholestatic hepatitis" can develop, which rapidly evolve to graft failure. The immunoglobin against the B virus and lamivudine reduce the risk of reinfection. The principal factor associated with reinfection is active viral replication before the transplantation, thus it is considered a contraindication for liver transplantation. INF-alpha has been used in the treatment of hepatitis B virus reinfection with discouraging results. More recently, lamivudine and adefovir have been used. Post-transplantation recurrence of hepatitis C is universal and its evolution towards cirrhosis is more rapid than in immunocompetent patients, with graft dysfunction being the most frequent cause of mortality and of indication for retransplantation. Different factors have been related to the severity of the recurrence including factors related to the donor, the recipient, the virus, immunosuppression and surgery. There are no preventive treatments against recurrence of post-transplantation hepatitis C. In the treatment of the hepatitis C virus recurrence, INF-alpha and rivabirin have been used in single form or in combination with variable results, with the combined therapy being more effective. Recently, encouraging results have been described with the combination of pegylated interferon and rivabirin without a higher incidence of rejection. Finally, the results of retransplantation in patients with recurrent hepatitis B or C have not been encouraging.

Hepatitis B↗

Conversion from calcineurin inhibitors to mycophenolate mofetil in liver transplant recipients with diabetes mellitus.

Diabetes mellitus, a frequent metabolic complication in liver transplant recipients, may be produced by the diabetogenic effect of calcineurin inhibitors cyclosporine and tacrolimus. The aim of this study was to investigate the safety and metabolic effects of a gradual switch from cyclosporine or tacrolimus to mycophenolate mofetil among 12 diabetic liver transplant recipients. One patient was withdrawn from the study due to gastrointestinal side effects. Of the 11 remaining patients, cyclosporine or tacrolimus was completely withdrawn in five patients. Two patients developed suspected acute rejection episodes that were controlled by increasing the tacrolimus dosage. Glycosylated hemoglobin A1C and C-peptide levels were significantly lower at 3 and 6 months after the initiation of mycophenolate mofetil (P<.03 in all cases). Furthermore, urea and uric acid levels were significantly reduced after the change of treatment. In conclusion, a switch from cyclosporine/tacrolimus to mycophenolate mofetil may produce beneficial metabolic effects in diabetic liver transplant recipients, but poses a risk of graft rejection.

Blood Glucose↗

Liver transplantation in cirrhotic patients with diabetes mellitus: midterm results, survival, and adverse events.

Liver cirrhosis is frequently associated with diabetes mellitus (DM), and this metabolic complication is also frequent after orthotopic liver transplantation (OLT). The aim of our study is to investigate which factors are associated with DM before and after OLT and their impact on post-OLT evolution. We evaluated the prevalence of DM among 115 liver transplant candidates with cirrhosis and assessed their evolution after OLT (median follow-up, 41 months). Sixteen candidates had DM requiring pharmacological therapy (group A), 45 candidates had DM controlled with diet (group B), and 54 candidates did not have DM (group C). One-year and 3-year actuarial survival rates were 100% and 100% for group A, 91% and 85% for group B, and 77% and 74% for group C, respectively (P <.03). Post-OLT DM was more frequent in group A. The incidence of other metabolic complications, major infections, rejection, and arterial hypertension; the need for hospitalization; and renal and graft function of patients in groups A, B, and C were similar. The only risk factor for DM 1 year after OLT on multivariate analysis was pre-OLT DM requiring pharmacological treatment. The incidence of complications, need for hospitalization, and renal and graft function 1 year after OLT for patients with post-OLT DM were similar to those of patients without post-OLT DM. In conclusion, patients with cirrhosis who have DM have a greater risk for post-OLT DM, but their midterm survival is not worse than the survival of those without DM.

Adult↗

Prognostic model for early acute rejection after liver transplantation.

Hepatic graft rejection is a common complication after liver transplantation (LT), with a maximum incidence within the first weeks. The identification of high-risk patients for early acute rejection (EAR) might be useful for clinicians. A series of 133 liver graft recipients treated with calcineurin inhibitors was retrospectively assessed to identify predisposing factors for EAR and develop a mathematical model to predict the individual risk of each patient. The incidence of EAR (< or =45 days after LT) was 35.3%. Multivariate analysis showed that recipient age, underlying liver disease, and Child's class before LT were independently associated with the development of EAR. Combining these 3 variables, the following risk score for the development of EAR was obtained: EAR score [F(x)] = 2.44 + (1.14 x hepatitis C virus cirrhosis) + (2.78 x immunologic cirrhosis) + (2.51 x metabolic cirrhosis)--(0.08 x recipient age in years) + (1.65 x Child's class A) [corrected]. Risk for rejection = e(F(x))/1 + e(F(x)). The combination of age, cause of liver disease, and Child's class may allow us to predict the risk for EAR.

Calcineurin Inhibitors↗

Influence of tumor characteristics on the outcome of liver transplantation among patients with liver cirrhosis and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) may recur after liver transplantation (LT), mainly in patients with multinodular and large tumors. However, factors predictive of outcome after LT in patients with small tumors remain ill defined. We investigated which factors were related to mortality or tumor recurrence among 47 liver transplant recipients with liver cirrhosis and HCC and compared them with 107 patients with liver cirrhosis without tumor who underwent LT in the same period. Patients with HCC were older (P <.001), more frequently had cirrhosis of a viral origin (P <.001), and had lower Child-Pugh scores (P <.001) than patients without tumor. Survival of patients with and without tumor was not significantly different (P =.20). Among patients with HCC, those with lower recurrence-free survival rates had liver cirrhosis of a viral origin, vascular invasion, bilobar disease, and tumor-node-metastasis (TNM) stage IV. At multivariate analysis, the only factor associated with mortality or recurrence was TNM stage IV (P =.02). Our results suggest that in patients with HCC and TNM stage IV, LT might be contraindicated.

Adult↗

Hyperhomocysteinemia in liver transplant recipients: prevalence and multivariate analysis of predisposing factors.

Liver transplant recipients have an increased risk for cardiovascular disease because of a high incidence of obesity, arterial hypertension, diabetes mellitus, and hyperlipidemia. Hyperhomocysteinemia has been found to be an important risk factor for cardiovascular disease in large studies. Fasting serum levels of homocysteine were measured in 105 liver transplant recipients, and hyperhomocysteinemia was defined as a fasting serum homocysteine level greater than 13 micromol/L. Patients with versus without hyperhomocysteinemia were compared. The possible association of hyperhomocysteinemia with age, sex, cause of liver disease, time elapsed since liver transplantation, immunosuppressive therapy, folic acid level, liver function test results, renal function, and other cardiovascular risk factors was investigated. Patients with serum homocysteine levels greater than 15 micromol/L were treated with folic acid, 10 mg/d, and serum homocysteine levels were measured again 1 to 3 months later in 10 patients. Hyperhomocysteinemia was detected in 28 patients (27%). In univariate analysis, it was associated with hepatitis C virus infection, treatment with mycophenolate mofetil, and greater serum levels of alkaline phosphatase, gamma-glutamyl transpeptidase, urea, and creatinine. In multivariate analysis, only greater serum levels of creatinine (P =.006) were associated with hyperhomocysteinemia. Treatment with folic acid resulted in a decrease in fasting serum homocysteine levels in 9 of the 10 patients tested (P =.01). Hyperhomocystinemia, associated with renal dysfunction, is a frequent finding in liver transplant recipients. Treatment with folic acid may reduce fasting homocysteine levels.

Creatinine↗

Pathological and virological findings in patients with persistent hypertransaminasaemia of unknown aetiology.

BACKGROUND: The histopathological spectrum and role of hepatitis viruses in cases of hypertransaminasaemia of unknown aetiology have not been correctly analysed in a sufficiently large number of patients. METHODS: We studied 1075 consecutive patients referred for liver biopsy because of elevation of alanine aminotransferase (ALT) levels for more than six months. From this population we selected those cases in whom the aetiology could not be defined from clinical, biochemical, and serological data obtained before biopsy. In these patients liver biopsies were reviewed, and hepatitis B virus (HBV)-DNA and hepatitis C virus (HCV)-RNA were assayed in serum by polymerase chain reaction (PCR). Serum hepatitis G virus (HGV)-RNA was determined by PCR in 74 patients. RESULTS: Of 1075 patients studied, the cause of the increased serum ALT levels remained elusive after appropriate testing in 109 patients (10.1%). Liver biopsies from these patients showed non-specific changes in 32.7% of cases, non-alcoholic steatohepatitis (NASH) in 15.8%, and chronic hepatitis or cirrhosis in 51.5%. HBV-DNA and/or HCV-RNA was detected more frequently in cryptogenic liver disease than in healthy blood donors (26.7% v 3.4%; p<0.001). HGV-RNA was found in only one patient. The proportion of cases with detectable HBV-DNA or HCV-RNA was 14.3% in patients with non-specific changes or NASH, 30.7% in patients with chronic hepatitis, and 61.5% in patients with cirrhosis. Cirrhosis was found more frequently in patients with positive HBV-DNA and/or HCV-RNA in serum than in those who tested negatively (p=0.005). CONCLUSIONS: In our series, patients in whom biochemical and serological data did not determine the aetiology of the disease represented 10% of all cases referred for liver biopsy for persistent elevation of serum transaminases. Approximately 50% of patients had chronic hepatitis or cirrhosis and the remainder had NASH or non-specific changes. Occult viral infections were found in a high proportion of cases in the first group and in a low percentage of patients in the second.

Alanine Transaminase↗

Aortic valve replacement with bioprostheses in liver transplant recipients.

Three cases of aortic valve replacement with porcine bioprostheses are reported in liver transplant recipients at two to six years after transplantation. Indications for aortic valve replacement (AVR) were aortic stenosis (n = 2) and aortic regurgitation (n = 1). The use of bioprostheses was recommended because of patient age, the need for multiple liver biopsies, and contraindication to the use of anticoagulation therapy. The patient who underwent AVR because of aortic regurgitation developed structural valve deterioration (SVD) during the next five years after surgery, and thus replacement of the bioprosthetic valve was required. Recipients of liver transplant who undergo valve replacement with tissue valves should be carefully followed up because of the risk of early SVD. AVR may be performed safely after liver transplantation.

Adult↗

Conversion of liver transplant recipients on cyclosporine with renal impairment to mycophenolate mofetil.

The management of liver transplant recipients with renal function impairment remains controversial because cyclosporine withdrawal from triple immunosuppression regimens may be followed by graft rejection. A nonnephrotoxic and powerful immunosuppressant such as mycophenolate mofetil (MMF) could allow a reduction of cyclosporine dosage or its withdrawal and an improvement in renal function in these patients. Eleven patients with serum creatinine levels greater than 1.5 mg/dL, normal graft function, and a rejection-free period of at least 1 year started MMF at a dose of 2000 mg/d (reduced in case of adverse events) while cyclosporine dosage was slowly reduced. At last follow-up (63 +/- 5 weeks), 7 patients remained free of cyclosporine (6 of those patients are also free of steroids), 2 patients reduced their cyclosporine dose, and 2 patients developed mild acute rejection that responded to a switch to tacrolimus therapy. Serum creatinine and urea levels in the 7 patients free of cyclosporine decreased from 2.22 +/- 0.13 to 1.90 +/- 0.19 mg/dL (P =.05) and 0.95 +/- 0.10 to 0.60 +/- 0.10 g/L (P <.001), respectively. Creatinine clearance increased from 38.16 +/- 5.60 to 47.01 +/- 6. 76 mL/min (P =.005). Control of arterial hypertension also improved. Tolerance to MMF was good, but 6 patients required dose reductions, mainly because of asymptomatic anemia. In conclusion, in liver transplant recipients with stable graft function, MMF may allow cyclosporine dose reduction or discontinuation, thus improving renal function and the control of arterial hypertension. This change of treatment must be carefully monitored because of the frequent need for MMF dose reduction and the risk for rejection.

Aged↗

Risk factors for recurrence of hepatitis C after liver transplantation.

Recurrent hepatitis C is a frequent complication after liver transplantation for hepatitis C virus-related cirrhosis, but risk factors related to its development remain ill defined. Twenty-three patients receiving a primary liver graft for hepatitis C virus-related cirrhosis and with an assessable biopsy performed at least 6 months after liver transplantation were studied retrospectively. The end point of this study was to look for risk factors associated with the development of histologic hepatitis C in the graft. Thirty-six major variables were studied, and those reaching significance by univariate analysis were included in a multivariate analysis. Eighteen patients (78%) developed posttransplant hepatitis C. On univariate analysis, six variables showed significant predictive value: increased immunosuppression for treatment of acute rejection; pretransplant hepatocellular carcinoma; cumulative doses of prednisone at 3, 6, and 12 months after transplantation; and mean blood trough levels of cyclosporine in the first 6 months posttransplantation. On multivariate analysis, two variables retained independent statistical significance as predictors of hepatitis C recurrence, namely receipt of antirejection therapy (P = .0087) and lower mean cyclosporine levels in the first 6 months after transplantation (P = .0134). Therefore, recurrence of hepatitis C after liver transplantation seems to be at least partially related to posttransplantation immunosuppressive therapy.

Adult↗

Liver transplantation in hepatitis C. A Spanish multi-centre experience.

OBJECTIVE: The purpose of this retrospective survey was to determine the prevalence and outcome of hepatitis C virus (HCV) infection in cirrhotic patients undergoing liver transplantation (OLT) in Spain in 1992. METHODS: Post-OLT HCV infection was defined by anti-HCV (second-generation ELISA) and/or PCR. Patients were divided into groups A (HCV-positive pre-OLT: n = 124, 46%) and B (HCV-negative pre-OLT: n = 145, 54%). RESULTS: HCV infection was more prevalent in patients originally diagnosed as having non-A non-B cirrhosis (97%) and cryptogenic cirrhosis (79%) than in patients with cholestatic or metabolic diseases. Group A patients were older (53.3+/-7.9 versus 47.6+/-9.7; P< 0.05) and had a higher prevalence of hepatocellular carcinoma (22% versus 4%, P< 0.05). Post-OLT HCV infection was 99% in group A versus 4% in group B (P< 0.05). Histological hepatitis developed in 39% (66% in group A versus 14% in group B, P< 0.05) with similar follow-up. Chronic rejection occurred in 6% (3% in group A versus 8.5% in group B, P= 0.07). Retransplantation rate (overall 8%) and two-year patient survival did not differ between groups (79% versus 72%). Graft survival was higher in group A (74% versus 65% at 2 years, P= 0.04). CONCLUSIONS: HCV-cirrhosis represented the most frequent indication for OLT in Spain in 1992. While HCV recurrence was universal, de novo acquisition was rare. HCV accounted for most post-OLT hepatitis (87%), but was not associated with chronic rejection, nor with a higher retransplantation rate. Patient survival was not different in HCV patients compared to a control group after a follow-up of 2-3 years. Therefore, at present, HCV-cirrhosis is an acceptable indication for OLT.

Adolescent↗

Liver transplantation in cirrhotic patients over 60 years of age.

Although life expectancy in Spain is above seventy years, age over sixty is considered a relative contraindication for liver transplantation (LT) in most centers. The aim of this study was to assess the outcome of LT in patients over sixty years of age comparing them to patients under that age. From January 1992 to August 1995, 61 cirrhotic patients underwent LT at our institution; of them, 43 (group I) were younger than 60 years (mean +/- SEM: 51.9 +/- 0.9 years, range: 37-59) and 18 patients (group II) were 60 years or older (64.1 +/- 0.7, range: 60-71). Main pre-transplant variables (sex, etiology of liver disease, presence of hepatocarcinoma, Child-Pugh's score and renal function) were similar in both groups. The follow-up (median and range) for group I was 28 and 3-47 months, and for group II 16.5 and 3-48 months. Actuarial survival rates at one and four years post-LT were respectively 88.3% and 85.6% for group I, and 87.8% and 87.8% for the group II (p = n.s.). There were no differences between both groups regarding the incidence of rejection, major infections, neurologic complications, renal failure, pathological bone fractures, diabetes mellitus or hypertension. Nevertheless, cardiovascular complications were significantly more frequent in group II (p = 0.002) although they were not the cause of death. In conclusion, our results show that the outcome of LT in patients over sixty years old is comparable to that observed in patients under that age. LT should not be contraindicated on the only basis of an age greater than 60 years.

Adult↗